Impact of Emergency Department Probiotic Treatment of Pediatric Gastroenteritis

急诊科益生菌治疗小儿胃肠炎的影响

• 批准号: 8782626
• 负责人: Stephen Bradley Freedman
• 金额: $ 72.92万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-10 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782626
• 关键词: Abdomen; Absenteeism; Accident and Emergency department; Acute; Adverse effects; Adverse event; Affect; Age-Months; Applied Research; Caregivers; Cessation of life; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical effectiveness; Collaborations; Consumption; Contracts; Cost Effectiveness Analysis; Cost Savings; Data; Dehydration; Developing Countries; Diarrhea; Disease; Double-Blind Method; Economic Burden; Economics; Effectiveness; Emergency Care; European; Family; Feces; Fever; Food Safety; Frequencies; Funding; Future; Gastroenteritis; Government Agencies; Growth; Guidelines; Health; Health Benefit; Health Care Visit; Healthcare; Healthcare Systems; Height; Hospitalization; Hospitalized Child; Immunologics; Infection; Infection Control; Institution; Intervention; Intestines; Knowledge; Lactobacillus casei rhamnosus; Life; Malnutrition; Manufacturer Name; Marketing; Medical; Methodology; Microbe; Modification; Morbidity - disease rate; Multicenter Studies; Outcome; Outcome Measure; Outpatients; Parents; Patients; Pediatric Hospitals; Physicians; Placebos; Policy Maker; Practice Guidelines; Prevention; Principal Investigator; Probiotics; Process; Prospective Studies; Public Health; Quality Control; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recommendation; Rehydrations; Reporting; Research; Resources; Role; Safety; Sample Size; Sampling; Serious Adverse Event; Severities; Societies; Solid; Solutions; Supportive care; Symptoms; Therapeutic Intervention; United States; United States Food and Drug Administration; Visit; Vomiting; Work; aged; authority; base; clinical practice; clinically relevant; cost; design; economic impact; improved; microbial; novel strategies; patient population; randomized placebo controlled trial; secondary infection; standard of care; symptom management; trend

DESCRIPTION (provided by applicant): Acute gastroenteritis (AGE) is a leading cause of malnutrition and death worldwide. In the US, close to 48 million people contract AGE and 128,000 are hospitalized each year . Episodes of AGE can result in substantial morbidity to children and their families. In addition, the costs to caregivers, the health-care system, and society are significant. At present, treatment options are limited and targeted at symptom management rather than disease modification. Probiotics - live microbial cultures which, when consumed in adequate amounts, confer documented health benefits - may be an ideal solution. They are hypothesized to work via a combination of direct microbiologic and immunologic mechanisms. Probiotics have shown promise in early clinical research in hospitalized children in developing countries. These early efforts are limited by small samples, outcomes lacking relevance to outpatients, poor methodology and absence of side effect reporting; thus, the potential role of probiotics remains poorly defined and practice guidelines do not endorse their use. There are current trends, however, that obligate an urgent assessment of these agents. First, probiotic manufacturers have embarked in aggressive public marketing strategies that make health claims that may not be supported by rigorous research, and the world-wide market for probiotic products is growing steadily (projected growth 2009-2014 12.6% for a total of US $32.6 billion/year). Second, government agencies (US FDA and European Food safety Authority (EFSA)) remain concerned about their value and safety. Third, some institutions are now recommending the use of probiotics based on potentially flawed or limited evidence. Fourth, parents of patients with AGE are often medicating their children without guidance from medical professionals. We are therefore concerned that probiotic consumption is increasing without solid evidence to support its use, which underscores the necessity to conduct a definitive trial without delay. Objectives - The overall objective of this multi-national randomized clinical trial is to determine if a specific probiotic agent, Lactobacillus rhamnosus GG(LGG), the most widely available, studied and regulated probiotic in the US, should routinely be administered to outpatient children who are suffering from AGE. The specific aims of this proposal are: (1) to determine the clinical effectiveness of LGG and (2) to determine the safety and side effect profile of LGG in children 3-48 months of age presenting to the Emergency Department (ED) with AGE. Study Setting & Design - The study will be conducted in 8 US pediatric emergency departments within the federally funded Pediatric Emergency Care Applied Research Network (PECARN). We will randomize 900 children to receive 5 days of a probiotic agent (LGG 1 x 1010 CFU twice a day) or placebo. The main outcome is the occurrence of moderate-severe disease as defined by the Modified Vesikari Score, a validated clinical severity score, which incorporates the frequency and duration of diarrhea, frequency and duration of vomiting, height of fever, need for future health-care visits and medical interventions provided. We will also assess the occurrence of adverse events and side effects related to the use of LGG. We will collect stool samples to conduct mechanism of action studies as well as economic data to conduct cost effectiveness analyses in the future. Impact - This study will directly inform clinica practice by providing the first definitive evidence to support recommendations for or against the routine use of probiotics in the treatment of pediatric AGE. In addition it will provide health-car practitioners and policy makers with (a) a clear picture on the potential side effects from probiotic use, and with the data collected (b) knowledge on the mechanism of action and (c) of the potential economic impact of probiotic use on health-care systems and society. Thus, the potential clinical and societal impacts of the proposed study are substantial and the results will guide the standard of care: if positive, guidelines will be able to endorse probiotic administratio with important positive consequences for the health of several million US children annually. Moreover, if beneficial the cost savings to the health-care system and society may be substantial. If the results are negative, a firm recommendation against the routine use of probiotics would be justified. Collaborators - This work is collaboration between leaders in multicenter and AGE research (Schnadower, Freedman, Tarr, Gorelick, Mahajan, Stanley, Roskind, Powell, O'Connel, Ruddy Chun, Levine and Casper) in prestigious Children's Hospitals within a federally funded multicenter network (PECARN) with a strong record in conducting high quality, high impact clinical trials.

描述(申请人提供)：急性胃肠炎(AGE)是全球营养不良和死亡的主要原因。在美国，每年有近4800万适龄人口和12.8万人住院。年龄段的发作可导致儿童及其家庭的严重发病率。此外，护理人员、医疗保健系统和社会的成本也是巨大的。目前，治疗选择有限，目标是症状管理，而不是疾病修改。益生菌--活的微生物培养物，当适量食用时，可以带来有据可查的健康益处--可能是一种理想的解决方案。它们被认为是通过直接微生物学和免疫学机制的组合发挥作用。益生菌在发展中国家住院儿童的早期临床研究中显示出了希望。这些早期努力受限于小样本、与门诊患者缺乏相关性的结果、糟糕的方法学以及缺乏副作用报告；因此，益生菌的潜在作用仍然定义不清，实践指南不支持使用它们。然而，目前的趋势要求对这些代理人进行紧急评估。首先，益生菌制造商已经开始积极的公共营销战略，提出可能得不到严格研究支持的健康主张，全球益生菌产品市场正在稳步增长(2009-2014年预计增长12.6%，总计326亿美元/年)。其次，政府机构(美国FDA和欧洲食品安全局(EFSA))仍然担心它们的价值和安全。第三，一些机构现在建议使用益生菌，理由是证据可能有缺陷或有限。第四，老年患者的父母经常在没有医疗专业人员指导的情况下给他们的孩子用药。因此，我们感到关切的是，在没有确凿证据支持益生菌使用的情况下，益生菌消费正在增加，这突出表明有必要毫不拖延地进行最终试验。目的：这项多国随机临床试验的总体目标是确定一种特定的益生菌制剂--鼠李糖乳杆菌GG(Lactobacillusrhamnosus GG)--美国可获得、研究和监管最广泛的益生菌--是否应该常规地应用于患有老年病的门诊儿童。这项建议的具体目的是：(1)确定LGG的临床有效性；(2)确定LGG在3-48个月大的儿童中随年龄增长而出现在急诊科(ED)的安全性和副作用。研究背景和设计--这项研究将在联邦资助的儿科急救应用研究网络(PECARN)内的8个美国儿科急诊科进行。我们将900名儿童随机分为两组，分别接受5天的益生菌制剂(LGG 1×1010 CFU，每天两次)或安慰剂治疗。主要结果是发生了由修正的Vesikari评分定义的中-重度疾病，这是一个经过验证的临床严重程度评分，其中包括腹泻的频率和持续时间、呕吐的频率和持续时间、发烧程度、是否需要未来的保健访问和提供的医疗干预。我们还将评估与使用LGG相关的不良事件和副作用的发生情况。我们会收集粪便样本，以进行行动机制研究，以及收集经济数据，以便日后进行成本效益分析。影响-这项研究将通过提供第一个确凿的证据来支持或反对在儿科年龄治疗中常规使用益生菌的建议，从而直接为Clinica实践提供信息。此外，它将为保健车从业者和政策制定者提供(A)关于使用益生菌的潜在副作用的清晰图景，以及(B)关于作用机制的知识和(C)关于使用益生菌对保健系统和社会的潜在经济影响的收集的数据。因此，拟议研究的潜在临床和社会影响是巨大的，结果将指导护理标准：如果是积极的，指南将能够支持益生菌管理，对每年数百万美国儿童的健康产生重要的积极影响。此外，如果有益，为卫生保健系统和社会节省的成本可能是巨大的。如果结果是否定的，那么反对常规使用益生菌的坚定建议将是合理的。合作者-这项工作是多中心和年龄研究的领导者(Schnadower、Freedman、Tarr、Gorelick、Mahajan、Stanley、Roskind、Powell、O‘Connel、Ruddy Chun、Levine和Casper)在联邦资助的多中心网络(PECARN)内的著名儿童医院之间的合作，在进行高质量、高影响的临床试验方面有着良好的记录。